Editing DNA (section)

== Properties ==
[[File:DNA chemical structure.svg|thumb|upright=1.35|Chemical structure of DNA; [[hydrogen bond]]s shown as dotted lines. Each end of the double helix has an exposed [[Directionality (molecular biology)#5′-end|5']] phosphate on one strand and an exposed [[Directionality (molecular biology)#3′-end|3′]] hydroxyl group (—OH) on the other.]]

DNA is a long [[polymer]] made from repeating units called [[nucleotide]]s.<ref>{{cite book | vauthors = Saenger W |title= Principles of Nucleic Acid Structure |publisher= Springer-Verlag |location= New York |year= 1984 |isbn= 0-387-90762-9}}</ref><ref name="Alberts">{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Peter W | title = Molecular Biology of the Cell | edition = Fourth | publisher = Garland Science | year = 2002 | location = New York and London | isbn = 0-8153-3218-1 | oclc = 145080076 | url = https://www.ncbi.nlm.nih.gov/books/NBK21054/ | url-status=live | archive-url = https://web.archive.org/web/20161101022040/https://www.ncbi.nlm.nih.gov/books/NBK21054/ | archive-date = 1 November 2016 | df = dmy-all }}</ref> The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes.<ref>{{cite journal | vauthors = Irobalieva RN, Fogg JM, Catanese DJ, Catanese DJ, Sutthibutpong T, Chen M, Barker AK, Ludtke SJ, Harris SA, Schmid MF, Chiu W, Zechiedrich L | title = Structural diversity of supercoiled DNA | journal = Nature Communications | volume = 6 | pages = 8440 | date = October 2015 | issue = 1 | pmid = 26455586 | pmc = 4608029 | doi = 10.1038/ncomms9440 | bibcode = 2015NatCo...6.8440I |issn=2041-1723 }}</ref> In all species it is composed of two helical chains, bound to each other by [[hydrogen bonds]]. Both chains are coiled around the same axis, and have the same [[Pitch (screw)|pitch]] of {{convert|34|Å|nm|lk=on}}. The pair of chains have a radius of {{cvt|10|Å|nm}}.<ref name="Watson-1953">{{cite journal | vauthors = Watson JD, Crick FH | title = Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid | journal = Nature | volume = 171 | issue = 4356 | pages = 737–38 | date = April 1953 | pmid = 13054692 | doi = 10.1038/171737a0 | url = http://www.nature.com/nature/dna50/watsoncrick.pdf | bibcode = 1953Natur.171..737W | s2cid = 4253007 | url-status=live | archive-url = https://web.archive.org/web/20070204110320/http://www.nature.com/nature/dna50/watsoncrick.pdf | archive-date = 4 February 2007 | df = dmy-all |issn=0028-0836 }}</ref> According to another study, when measured in a different solution, the DNA chain measured {{cvt|22|-|26|Å|nm}} wide, and one nucleotide unit measured {{cvt|3.3|Å|nm}} long.<ref>{{cite journal | vauthors = Mandelkern M, Elias JG, Eden D, Crothers DM | title = The dimensions of DNA in solution | journal = Journal of Molecular Biology | volume = 152 | issue = 1 | pages = 153–61 | date = October 1981 | pmid = 7338906 | doi = 10.1016/0022-2836(81)90099-1|issn=0022-2836 }}</ref> The buoyant density of most DNA is 1.7g/cm<sup>3</sup>.<ref>{{cite journal |last1=Arrighi |first1=Frances E. |last2=Mandel |first2=Manley |last3=Bergendahl |first3=Janet |last4=Hsu |first4=T. C. |title=Buoyant densities of DNA of mammals |journal=Biochemical Genetics |date=June 1970 |volume=4 |issue=3 |pages=367–376 |doi=10.1007/BF00485753|pmid=4991030 |s2cid=27950750 |issn=0006-2928 }}</ref>

DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together.<ref name="Watson-1953" /><ref name=berg>{{cite book | vauthors = Berg J, Tymoczko J, Stryer L | date = 2002 | title = Biochemistry | publisher = W.H. Freeman and Company | isbn = 0-7167-4955-6 }}</ref> These two long strands coil around each other, in the shape of a [[double helix]]. The nucleotide contains both a segment of the [[Backbone chain|backbone]] of the molecule (which holds the chain together) and a [[nucleobase]] (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a [[nucleoside]], and a base linked to a sugar and to one or more phosphate groups is called a [[nucleotide]]. A [[biopolymer]] comprising multiple linked nucleotides (as in DNA) is called a [[polynucleotide]].<ref name="IUPAC">{{cite journal | author = IUPAC-IUB Commission on Biochemical Nomenclature (CBN) | title = Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents. Recommendations 1970 | journal = The Biochemical Journal | volume = 120 | issue = 3 | pages = 449–54 | date = December 1970 | pmid = 5499957 | pmc = 1179624 | doi = 10.1042/bj1200449 | url = http://www.chem.qmul.ac.uk/iupac/misc/naabb.html | archive-url = https://web.archive.org/web/20070205191106/http://www.chem.qmul.ac.uk/iupac/misc/naabb.html | url-status=dead | archive-date = 5 February 2007 |issn=0306-3283 }}</ref>

The backbone of the DNA strand is made from alternating [[phosphate]] and [[carbohydrate|sugar]] groups.<ref name=Ghosh>{{cite journal | vauthors = Ghosh A, Bansal M | title = A glossary of DNA structures from A to Z | journal = Acta Crystallographica Section D | volume = 59 | issue = Pt 4 | pages = 620–26 | date = April 2003 | pmid = 12657780 | doi = 10.1107/S0907444903003251| bibcode = 2003AcCrD..59..620G |issn=0907-4449 }}</ref> The sugar in DNA is [[deoxyribose|2-deoxyribose]], which is a [[pentose]] (five-[[carbon]]) sugar. The sugars are joined by phosphate groups that form [[phosphodiester bond]]s between the third and fifth carbon [[atom]]s of adjacent sugar rings. These are known as the [[Directionality (molecular biology)#3′-end|3′-end]] (three prime end), and [[Directionality (molecular biology)#5′-end|5′-end]] (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a [[glycosidic bond]].<ref name="berg" />

Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers [[directionality (molecular biology)|directionality]] (sometimes called polarity) to each DNA strand. In a [[nucleic acid double helix]], the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are [[Antiparallel (biochemistry)|antiparallel]]. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and [[RNA]] is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar [[ribose]] in RNA.<ref name="berg" />

[[File:DNA animation.gif|thumb|upright|A section of DNA. The bases lie horizontally between the two spiraling strands<ref>{{Cite web| vauthors = Edwards KJ, Brown DG, Spink N, Skelly JV, Neidle S |title=RCSB PDB – 1D65: Molecular structure of the B-DNA dodecamer d(CGCAAATTTGCG)2. An examination of propeller twist and minor-groove water structure at 2.2 A resolution.|url=https://www.rcsb.org/structure/1D65|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref> ([[:File:DNA orbit animated.gif|animated version]]).]]

The DNA double helix is stabilized primarily by two forces: [[hydrogen bond]]s between nucleotides and [[Stacking (chemistry)|base-stacking]] interactions among [[aromatic]] nucleobases.<ref name="Yakovchuk2006">{{cite journal | vauthors = Yakovchuk P, Protozanova E, Frank-Kamenetskii MD | title = Base-stacking and base-pairing contributions into thermal stability of the DNA double helix | journal = Nucleic Acids Research | volume = 34 | issue = 2 | pages = 564–74 | year = 2006 | pmid = 16449200 | pmc = 1360284 | doi = 10.1093/nar/gkj454 |issn=0305-1048 }}</ref> The four bases found in DNA are [[adenine]] ({{mono|A}}), [[cytosine]] ({{mono|C}}), [[guanine]] ({{mono|G}}) and [[thymine]] ({{mono|T}}). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for [[adenosine monophosphate]]. Adenine pairs with thymine and guanine pairs with cytosine, forming {{mono|A-T}} and {{mono|G-C}} [[base pair]]s.<ref>{{cite book | vauthors = Tropp BE | title = Molecular Biology | edition = 4th | year = 2012 | publisher = Jones and Barlett Learning | location = Sudbury, Mass. | isbn = 978-0-7637-8663-2 }}</ref><ref>{{cite web | url = https://www.mun.ca/biology/scarr/Watson-Crick_Model.html | title = Watson-Crick Structure of DNA | year = 1953 | vauthors = Carr S | publisher = Memorial University of Newfoundland | access-date=13 July 2016 | url-status=live | archive-url = https://web.archive.org/web/20160719095721/http://www.mun.ca/biology/scarr/Watson-Crick_Model.html | archive-date = 19 July 2016 | df = dmy-all }}</ref>

=== Nucleobase classification ===
The nucleobases are classified into two types: the [[purine]]s, {{mono|A}} and {{mono|G}}, which are fused five- and six-membered [[heterocyclic compound]]s, and the [[pyrimidine]]s, the six-membered rings {{mono|C}} and {{mono|T}}.<ref name=berg /> A fifth pyrimidine nucleobase, [[uracil]] ({{mono|U}}), usually takes the place of thymine in RNA and differs from thymine by lacking a [[methyl group]] on its ring. In addition to RNA and DNA, many artificial [[nucleic acid analogue]]s have been created to study the properties of nucleic acids, or for use in biotechnology.<ref>{{cite journal | vauthors = Verma S, Eckstein F | title = Modified oligonucleotides: synthesis and strategy for users | journal = Annual Review of Biochemistry | volume = 67 | pages = 99–134 | year = 1998 | pmid = 9759484 |issn=0066-4154 | doi = 10.1146/annurev.biochem.67.1.99 | doi-access = free }}</ref>

=== Non-canonical bases ===

Modified bases occur in DNA. The first of these recognized was [[5-methylcytosine]], which was found in the [[genome]] of ''[[Mycobacterium tuberculosis]]'' in 1925.<ref name=Johnson1925>{{cite journal | vauthors = Johnson TB, Coghill RD | year = 1925 | title = Pyrimidines. CIII. The discovery of 5-methylcytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus. | journal = Journal of the American Chemical Society | volume = 47 | pages = 2838–44 | doi=10.1021/ja01688a030|issn=0002-7863}}</ref> The reason for the presence of these noncanonical bases in bacterial viruses ([[bacteriophage]]s) is to avoid the [[restriction enzyme]]s present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses.<ref name="pmid27319741">{{cite journal |vauthors=Weigele P, Raleigh EA |title=Biosynthesis and Function of Modified Bases in Bacteria and Their Viruses |journal=Chemical Reviews |volume=116 |issue=20 |pages=12655–12687 |date=October 2016 |pmid=27319741 |doi=10.1021/acs.chemrev.6b00114 |doi-access=free |issn=0009-2665 }}</ref> Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the [[epigenetics|epigenetic]] control of gene expression in plants and animals.<ref name="pmid30619465">{{cite journal |vauthors=Kumar S, Chinnusamy V, Mohapatra T |title=Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond |journal=Frontiers in Genetics |volume=9 |pages=640 |date=2018 |pmid=30619465 |pmc=6305559 |doi=10.3389/fgene.2018.00640 |issn=1664-8021 |doi-access=free }}</ref>

A number of noncanonical bases are known to occur in DNA.<ref name="pmid28941008">{{cite journal | vauthors = Carell T, Kurz MQ, Müller M, Rossa M, Spada F | title = Non-canonical Bases in the Genome: The Regulatory Information Layer in DNA | journal = Angewandte Chemie | volume = 57 | issue = 16 | pages = 4296–4312 | date = April 2018 | pmid = 28941008 | doi = 10.1002/anie.201708228 }}</ref> Most of these are modifications of the canonical bases plus uracil.

* Modified '''Adenine'''
** N6-carbamoyl-methyladenine
** N6-methyadenine
* Modified '''Guanine'''
** 7-Deazaguanine
** 7-Methylguanine
* Modified '''Cytosine'''
** N4-Methylcytosine
** 5-Carboxylcytosine
** 5-Formylcytosine
** 5-Glycosylhydroxymethylcytosine
** 5-Hydroxycytosine
** 5-Methylcytosine
* Modified '''Thymidine'''
** α-Glutamythymidine
** α-Putrescinylthymine
* '''Uracil''' and modifications
** [[Base J]]
** Uracil
** 5-Dihydroxypentauracil
** 5-Hydroxymethyldeoxyuracil
* Others
** Deoxyarchaeosine
** 2,6-Diaminopurine (2-Aminoadenine)

=== Grooves ===
[[File:DNA-ligand-by-Abalone.png|thumb|DNA major and minor grooves. The latter is a binding site for the [[Hoechst stain]] dye 33258.]]

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a [[binding site]]. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. The major groove is {{convert|22|Å|nm}} wide, while the minor groove is {{cvt|12|Å|nm}} in width.<ref>{{cite journal | vauthors = Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson RE | title = Crystal structure analysis of a complete turn of B-DNA | journal = Nature | volume = 287 | issue = 5784 | pages = 755–58 | date = October 1980 | pmid = 7432492 | doi = 10.1038/287755a0 | bibcode = 1980Natur.287..755W | s2cid = 4315465 }}</ref> Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as [[transcription factor]]s that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.<ref name="Pabo1984">{{cite journal | vauthors = Pabo CO, Sauer RT | title = Protein-DNA recognition | journal = Annual Review of Biochemistry | volume = 53 | pages = 293–321 | year = 1984 | pmid = 6236744 | doi = 10.1146/annurev.bi.53.070184.001453 }}</ref> This situation varies in unusual conformations of DNA within the cell ''(see below)'', but the major and minor grooves are always named to reflect the differences in width that would be seen if the DNA was twisted back into the ordinary [[B-DNA|B form]].

=== Base pairing ===
{{further|Base pair}}
<div class="thumb tright" style="background:#f9f9f9; border:1px solid #ccc; margin:0.5em;">
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<div style="border: none; width:282px;"><div class="thumbcaption">Top, a '''{{mono|GC}}''' base pair with three [[hydrogen bond]]s. Bottom, an '''{{mono|AT}}''' base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.</div></div></div>

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called [[Complementarity (molecular biology)|complementary]] [[base pair]]ing. Purines form [[hydrogen bond]]s to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high [[GC-content]] is more stable than DNA with low {{mono|GC}}-content. A [[Hoogsteen base pair]] (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing.<ref name="pmid23818176">{{cite journal |vauthors=Nikolova EN, Zhou H, Gottardo FL, Alvey HS, Kimsey IJ, Al-Hashimi HM |title=A historical account of Hoogsteen base-pairs in duplex DNA |journal=Biopolymers |volume=99 |issue=12 |pages=955–68 |year=2013 |pmid=23818176 |pmc=3844552 |doi=10.1002/bip.22334 }}</ref> As hydrogen bonds are not [[covalent bond|covalent]], they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high [[temperature]].<ref>{{cite journal | vauthors = Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub HE | title = Mechanical stability of single DNA molecules | journal = Biophysical Journal | volume = 78 | issue = 4 | pages = 1997–2007 | date = April 2000 | pmid = 10733978 | pmc = 1300792 | doi = 10.1016/S0006-3495(00)76747-6 | bibcode = 2000BpJ....78.1997C }}</ref> As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.<ref name=Alberts />

{{Anchor|ssDNA}}

==== ssDNA vs. dsDNA ====
Most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for {{mono|G,C}} stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high [[pH]] (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the {{mono|GC}}-content (% {{mono|G,C}} basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the [[DNA melting|melting temperature]] (also called ''T<sub>m</sub>'' value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of {{mono|GC}} base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high {{mono|GC}}-content have more strongly interacting strands, while short helices with high {{mono|AT}} content have more weakly interacting strands.<ref>{{cite journal | vauthors = Chalikian TV, Völker J, Plum GE, Breslauer KJ | title = A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 14 | pages = 7853–58 | date = July 1999 | pmid = 10393911 | pmc = 22151 | doi = 10.1073/pnas.96.14.7853 | bibcode = 1999PNAS...96.7853C | doi-access = free }}</ref> In biology, parts of the DNA double helix that need to separate easily, such as the {{mono|TATAAT}} [[Pribnow box]] in some [[promoter (biology)|promoters]], tend to have a high {{mono|AT}} content, making the strands easier to pull apart.<ref>{{cite journal | vauthors = deHaseth PL, Helmann JD | title = Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA | journal = Molecular Microbiology | volume = 16 | issue = 5 | pages = 817–24 | date = June 1995 | pmid = 7476180 | doi = 10.1111/j.1365-2958.1995.tb02309.x | s2cid = 24479358 }}</ref>

In the laboratory, the strength of this interaction can be measured by finding the melting temperature ''T<sub>m</sub>'' necessary to break half of the hydrogen bonds. When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.<ref>{{cite journal | vauthors = Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J | title = Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern | journal = Biochemistry | volume = 43 | issue = 51 | pages = 15996–6010 | date = December 2004 | pmid = 15609994 | doi = 10.1021/bi048221v | url = http://www.boc.uu.se/boc14www/thesis/johan2005/Paper%20V/Paper%20V.pdf | url-status=live | archive-url = https://web.archive.org/web/20070610205112/http://www.boc.uu.se/boc14www/thesis/johan2005/Paper%20V/Paper%20V.pdf | archive-date = 10 June 2007 | df = dmy-all }}</ref>

=== Amount ===
[[File:Human karyotype with bands and sub-bands.png|thumb|Schematic [[karyotype|karyogram]] of a human. It shows 22 [[homologous chromosome]]s, both the female (XX) and male (XY) versions of the [[sex chromosome]] (bottom right), as well as the [[human mitochondrial genetics|mitochondrial genome]] (to scale at bottom left). The blue scale to the left of each chromosome pair (and the mitochondrial genome) shows its length in terms of millions of DNA [[base pair]]s.{{further|Karyotype}}]]
In humans, the total female [[diploid]] [[nuclear genome]] per cell extends for 6.37 Gigabase pairs (Gbp), is 208.23&nbsp;cm long and weighs 6.51 picograms (pg).<ref name="pmid30813969">{{cite journal| vauthors=Piovesan A, Pelleri MC, Antonaros F, Strippoli P, Caracausi M, Vitale L| title=On the length, weight and GC content of the human genome. | journal=BMC Res Notes | year= 2019 | volume= 12 | issue= 1 | pages= 106 | pmid=30813969 | doi=10.1186/s13104-019-4137-z | pmc=6391780 | doi-access=free }}</ref> Male values are 6.27 Gbp, 205.00&nbsp;cm, 6.41 pg.<ref name="pmid30813969"/> Each DNA polymer can contain hundreds of millions of nucleotides, such as in [[chromosome 1]]. Chromosome 1 is the largest human [[chromosome]] with approximately 220 million [[base pair]]s, and would be {{val|85|u=mm}} long if straightened.<ref name="Gregory_2006" />

In [[eukaryote]]s, in addition to [[nuclear DNA]], there is also [[mitochondrial DNA]] (mtDNA) which encodes certain proteins used by the mitochondria. The mtDNA is usually relatively small in comparison to the nuclear DNA. For example, the [[Human mitochondrial genetics|human mitochondrial DNA]] forms closed circular molecules, each of which contains 16,569<ref name="Anderson_1981">{{cite journal | vauthors = Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG | display-authors = 6 | title = Sequence and organization of the human mitochondrial genome | journal = Nature | volume = 290 | issue = 5806 | pages = 457–465 | date = April 1981 | pmid = 7219534 | doi = 10.1038/290457a0 | s2cid = 4355527 | bibcode = 1981Natur.290..457A }}</ref><ref>{{Cite web |url=http://chemistry.umeche.maine.edu/CHY431/MitoDNA.html |title=Untitled |access-date=2012-06-13 |archive-url=https://web.archive.org/web/20110813123936/http://chemistry.umeche.maine.edu/CHY431/MitoDNA.html |archive-date=2011-08-13 |url-status=dead }}</ref> DNA base pairs,<ref name=Satoh1991>{{cite journal | vauthors = Satoh M, Kuroiwa T | title = Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell | journal = Experimental Cell Research | volume = 196 | issue = 1 | pages = 137–140 | date = September 1991 | pmid = 1715276 | doi = 10.1016/0014-4827(91)90467-9 }}</ref> with each such molecule normally containing a full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules.<ref name=Satoh1991/> Each human [[Cell (biology)|cell]] contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500.<ref name=Satoh1991/> However, the amount of mitochondria per cell also varies by cell type, and an [[egg cell]] can contain 100,000 mitochondria, corresponding to up to 1,500,000 copies of the mitochondrial genome (constituting up to 90% of the DNA of the cell).<ref name="pmid28721182">{{cite journal | vauthors = Zhang D, Keilty D, Zhang ZF, Chian RC | title = Mitochondria in oocyte aging: current understanding | journal = Facts, Views & Vision in ObGyn | volume = 9 | issue = 1 | pages = 29–38 | date = March 2017 | pmid = 28721182 | pmc = 5506767 }}</ref>

=== Sense and antisense ===
{{further|Sense (molecular biology)}}
{{redirect|Sense and antisense|the TV episode|Sense and Antisense (Millennium)}}
A [[DNA sequencing|DNA sequence]] is called a "sense" sequence if it is the same as that of a [[messenger RNA]] copy that is translated into protein.<ref>[http://www.chem.qmul.ac.uk/iubmb/newsletter/misc/DNA.html Designation of the two strands of DNA] {{Webarchive|url=https://web.archive.org/web/20080424015915/http://www.chem.qmul.ac.uk/iubmb/newsletter/misc/DNA.html |date=24 April 2008 }} JCBN/NC-IUB Newsletter 1989. Retrieved 7 May 2008</ref> The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.<ref>{{cite journal | vauthors = Hüttenhofer A, Schattner P, Polacek N | title = Non-coding RNAs: hope or hype? | journal = Trends in Genetics | volume = 21 | issue = 5 | pages = 289–97 | date = May 2005 | pmid = 15851066 | doi = 10.1016/j.tig.2005.03.007 }}</ref> One proposal is that antisense RNAs are involved in regulating [[gene expression]] through RNA-RNA base pairing.<ref>{{cite journal | vauthors = Munroe SH | title = Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns | journal = Journal of Cellular Biochemistry | volume = 93 | issue = 4 | pages = 664–71 | date = November 2004 | pmid = 15389973 | doi = 10.1002/jcb.20252 | s2cid = 23748148 }}</ref>

A few DNA sequences in prokaryotes and eukaryotes, and more in [[plasmid]]s and [[virus]]es, blur the distinction between sense and antisense strands by having [[overlapping gene]]s.<ref>{{cite journal | vauthors = Makalowska I, Lin CF, Makalowski W | title = Overlapping genes in vertebrate genomes | journal = Computational Biology and Chemistry | volume = 29 | issue = 1 | pages = 1–12 | date = February 2005 | pmid = 15680581 | doi = 10.1016/j.compbiolchem.2004.12.006 }}</ref> In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In [[bacteria]], this overlap may be involved in the regulation of gene transcription,<ref>{{cite journal | vauthors = Johnson ZI, Chisholm SW | title = Properties of overlapping genes are conserved across microbial genomes | journal = Genome Research | volume = 14 | issue = 11 | pages = 2268–72 | date = November 2004 | pmid = 15520290 | pmc = 525685 | doi = 10.1101/gr.2433104 }}</ref> while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.<ref>{{cite journal | vauthors = Lamb RA, Horvath CM | title = Diversity of coding strategies in influenza viruses | journal = Trends in Genetics | volume = 7 | issue = 8 | pages = 261–66 | date = August 1991 | pmid = 1771674 | doi = 10.1016/0168-9525(91)90326-L | pmc = 7173306 }}</ref>

=== Supercoiling ===
{{further|DNA supercoil}}

DNA can be twisted like a rope in a process called [[DNA supercoil]]ing. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.<ref>{{cite journal | vauthors = Benham CJ, Mielke SP | s2cid = 1427671 | title = DNA mechanics | journal = Annual Review of Biomedical Engineering | volume = 7 | pages = 21–53 | year = 2005 | pmid = 16004565 | doi = 10.1146/annurev.bioeng.6.062403.132016 | url = http://pdfs.semanticscholar.org/ab63/d57290ebf9bc3536fd3f2257a2b509076fc1.pdf | archive-url = https://web.archive.org/web/20190301225243/http://pdfs.semanticscholar.org/ab63/d57290ebf9bc3536fd3f2257a2b509076fc1.pdf | url-status = dead | archive-date = 1 March 2019 }}</ref> If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by [[enzyme]]s called [[topoisomerase]]s.<ref name=Champoux>{{cite journal | vauthors = Champoux JJ | s2cid = 18144189 | title = DNA topoisomerases: structure, function, and mechanism | journal = Annual Review of Biochemistry | volume = 70 | pages = 369–413 | year = 2001 | pmid = 11395412 | doi = 10.1146/annurev.biochem.70.1.369 }}</ref> These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as [[transcription (genetics)|transcription]] and [[DNA replication]].<ref name=Wang>{{cite journal | vauthors = Wang JC | title = Cellular roles of DNA topoisomerases: a molecular perspective | journal = Nature Reviews Molecular Cell Biology | volume = 3 | issue = 6 | pages = 430–40 | date = June 2002 | pmid = 12042765 | doi = 10.1038/nrm831 | s2cid = 205496065 }}</ref>

=== Alternative DNA structures ===
{{further|Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid|Molecular models of DNA|DNA structure}}
[[File:Dnaconformations.png|thumb|right|From left to right, the structures of [[A-DNA|A]], [[B-DNA|B]] and [[Z-DNA]]]]

DNA exists in many possible [[Conformational isomerism|conformations]] that include [[A-DNA]], [[B-DNA]], and [[Z-DNA]] forms, although only B-DNA and Z-DNA have been directly observed in functional organisms.<ref name=Ghosh /> The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal [[ion]]s, and the presence of [[polyamine]]s in solution.<ref>{{cite journal | vauthors = Basu HS, Feuerstein BG, Zarling DA, Shafer RH, Marton LJ | title = Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies | journal = Journal of Biomolecular Structure & Dynamics | volume = 6 | issue = 2 | pages = 299–309 | date = October 1988 | pmid = 2482766 | doi = 10.1080/07391102.1988.10507714 }}</ref>

The first published reports of A-DNA [[X-ray diffraction patterns]]—and also B-DNA—used analyses based on [[Patterson function]]s that provided only a limited amount of structural information for oriented fibers of DNA.<ref>
* {{cite journal |vauthors=Franklin RE, Gosling RG |title=The Structure of Sodium Thymonucleate Fibres I. The Influence of Water Content |journal=Acta Crystallogr |volume=6 |issue=8–9 |pages=673–77 |date=6 March 1953 |doi=10.1107/S0365110X53001939 |bibcode=1953AcCry...6..673F |url=http://journals.iucr.org/q/issues/1953/08-09/00/a00979/a00979.pdf |url-status=live |archive-url=https://web.archive.org/web/20160109043915/http://journals.iucr.org/q/issues/1953/08-09/00/a00979/a00979.pdf |archive-date=9 January 2016 |doi-access=free }}
* {{cite journal |vauthors=Franklin RE, Gosling RG |title=The structure of sodium thymonucleate fibres. II. The cylindrically symmetrical Patterson function |journal=Acta Crystallogr |volume=6 |issue=8–9 |pages=678–85 |year=1953|doi=10.1107/S0365110X53001940|bibcode=1953AcCry...6..678F |url=http://journals.iucr.org/q/issues/1953/08-09/00/a00980/a00980.pdf |archive-url=https://web.archive.org/web/20170629084321/http://journals.iucr.org/q/issues/1953/08-09/00/a00980/a00980.pdf |archive-date=2017-06-29 |url-status=live |doi-access=free }}</ref><ref name=NatFranGos>{{cite journal | vauthors = Franklin RE, Gosling RG | title = Molecular configuration in sodium thymonucleate | journal = Nature | volume = 171 | issue = 4356 | pages = 740–41 | date = April 1953 | pmid = 13054694 | doi = 10.1038/171740a0 | url = http://www.nature.com/nature/dna50/franklingosling.pdf | bibcode = 1953Natur.171..740F | s2cid = 4268222 | url-status=live | archive-url = https://web.archive.org/web/20110103160712/http://www.nature.com/nature/dna50/franklingosling.pdf | archive-date = 3 January 2011 | df = dmy-all }}</ref> An alternative analysis was proposed by Wilkins ''et al.'' in 1953 for the ''[[in vivo]]'' B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of [[Bessel function]]s.<ref name=NatWilk>{{cite journal | vauthors = Wilkins MH, Stokes AR, Wilson HR | title = Molecular structure of deoxypentose nucleic acids | journal = Nature | volume = 171 | issue = 4356 | pages = 738–40 | date = April 1953 | pmid = 13054693 | doi = 10.1038/171738a0 | url = http://www.nature.com/nature/dna50/wilkins.pdf | bibcode = 1953Natur.171..738W | s2cid = 4280080 | url-status=live | archive-url = https://web.archive.org/web/20110513234223/http://www.nature.com/nature/dna50/wilkins.pdf | archive-date = 13 May 2011 | df = dmy-all }}</ref> In the same journal, [[James Watson]] and [[Francis Crick]] presented their [[Molecular models of DNA|molecular modeling]] analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix.<ref name="Watson-1953" />

Although the ''B-DNA form'' is most common under the conditions found in cells,<ref>{{cite journal | vauthors = Leslie AG, Arnott S, Chandrasekaran R, Ratliff RL | title = Polymorphism of DNA double helices | journal = Journal of Molecular Biology | volume = 143 | issue = 1 | pages = 49–72 | date = October 1980 | pmid = 7441761 | doi = 10.1016/0022-2836(80)90124-2 }}</ref> it is not a well-defined conformation but a family of related DNA conformations<ref>{{cite journal|vauthors=Baianu IC|s2cid=189888972|year=1980|title=Structural Order and Partial Disorder in Biological systems|url=http://cogprints.org/3822/|journal=Bull. Math. Biol.|volume=42|issue=4|pages=137–41|doi=10.1007/BF02462372}}</ref> that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular [[Paracrystalline|paracrystals]] with a significant degree of disorder.<ref>{{cite book | vauthors = Hosemann R, Bagchi RN | title = Direct analysis of diffraction by matter | publisher = North-Holland Publishers | location = Amsterdam&nbsp;– New York | year = 1962 }}</ref><ref>{{cite journal|vauthors=Baianu IC|title=X-ray scattering by partially disordered membrane systems|journal=Acta Crystallogr A|volume=34|issue=5|pages=751–53|year=1978|doi=10.1107/S0567739478001540|bibcode=1978AcCrA..34..751B|url=http://journals.iucr.org/a/issues/1978/05/00/a15615/a15615.pdf|access-date=29 August 2019|archive-date=14 March 2020|archive-url=https://web.archive.org/web/20200314050140/http://journals.iucr.org/a/issues/1978/05/00/a15615/a15615.pdf|url-status=dead}}</ref>

Compared to B-DNA, the A-DNA form is a wider [[Helix#Properties and types|right-handed]] spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.<ref>{{cite journal | vauthors = Wahl MC, Sundaralingam M | title = Crystal structures of A-DNA duplexes | journal = Biopolymers | volume = 44 | issue = 1 | pages = 45–63 | year = 1997 | pmid = 9097733 | doi = 10.1002/(SICI)1097-0282(1997)44:1<45::AID-BIP4>3.0.CO;2-# }}</ref><ref>{{cite journal | vauthors = Lu XJ, Shakked Z, Olson WK | title = A-form conformational motifs in ligand-bound DNA structures | journal = Journal of Molecular Biology | volume = 300 | issue = 4 | pages = 819–40 | date = July 2000 | pmid = 10891271 | doi = 10.1006/jmbi.2000.3690 }}</ref> Segments of DNA where the bases have been chemically modified by [[methylation]] may undergo a larger change in conformation and adopt the [[Z-DNA|Z form]]. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.<ref>{{cite journal | vauthors = Rothenburg S, Koch-Nolte F, Haag F | title = DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles | journal = Immunological Reviews | volume = 184 | pages = 286–98 | date = December 2001 | pmid = 12086319 | doi = 10.1034/j.1600-065x.2001.1840125.x | s2cid = 20589136 }}</ref> These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.<ref>{{cite journal | vauthors = Oh DB, Kim YG, Rich A | title = Z-DNA-binding proteins can act as potent effectors of gene expression in vivo | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16666–71 | date = December 2002 | pmid = 12486233 | pmc = 139201 | doi = 10.1073/pnas.262672699 | bibcode = 2002PNAS...9916666O | doi-access = free }}</ref>

=== Alternative DNA chemistry ===
{{further|hypothetical types of biochemistry}}
For many years, [[Astrobiology|exobiologists]] have proposed the existence of a [[shadow biosphere]], a postulated microbial [[biosphere]] of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use [[Arsenic DNA|arsenic instead of phosphorus in DNA]]. A report in 2010 of the possibility in the [[bacterium]] [[GFAJ-1]] was announced,<ref name='arsenic extremophile'>{{cite news | vauthors = Palmer J |title=Arsenic-loving bacteria may help in hunt for alien life |date=2 December 2010 |url=https://www.bbc.co.uk/news/science-environment-11886943 |work=BBC News |access-date=2 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101203045804/http://www.bbc.co.uk/news/science-environment-11886943 |archive-date=3 December 2010 }}</ref><ref name="Space">{{cite news | vauthors = Bortman H |title=Arsenic-Eating Bacteria Opens New Possibilities for Alien Life |date=2 December 2010 |url=http://www.space.com/scienceastronomy/arsenic-bacteria-alien-life-101202.html |website=Space.com |access-date=2 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101204235915/http://www.space.com/scienceastronomy/arsenic-bacteria-alien-life-101202.html |archive-date=4 December 2010 }}</ref> though the research was disputed,<ref name="Space" /><ref>{{cite journal | vauthors = Katsnelson A |title=Arsenic-eating microbe may redefine chemistry of life |date=2 December 2010 |url=http://www.nature.com/news/2010/101202/full/news.2010.645.html |journal=Nature News |doi=10.1038/news.2010.645 |url-status=live |archive-url=https://web.archive.org/web/20120212155007/http://www.nature.com/news/2010/101202/full/news.2010.645.html |archive-date=12 February 2012 }}</ref> and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.<ref name="Nature">{{cite journal | vauthors = Cressey D |s2cid=87341731 |title='Arsenic-life' Bacterium Prefers Phosphorus after all |date=3 October 2012 |journal=Nature News |doi=10.1038/nature.2012.11520}}</ref>

=== Quadruplex structures ===
{{further|G-quadruplex}}
[[File:Parallel telomere quadruple.png|thumb|right|DNA quadruplex formed by [[telomere]] repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions.<ref>{{Cite web|title=Structure and packing of human telomeric DNA|url=http://ndbserver.rutgers.edu/service/ndb/atlas/summary?searchTarget=UD0017|access-date=2023-05-18|website=ndbserver.rutgers.edu}}</ref>]]

At the ends of the linear chromosomes are specialized regions of DNA called [[telomere]]s. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme [[telomerase]], as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes.<ref name=Greider>{{cite journal | vauthors = Greider CW, Blackburn EH | title = Identification of a specific telomere terminal transferase activity in Tetrahymena extracts | journal = Cell | volume = 43 | issue = 2 Pt 1 | pages = 405–13 | date = December 1985 | pmid = 3907856 | doi = 10.1016/0092-8674(85)90170-9 | doi-access = free }}</ref> These specialized chromosome caps also help protect the DNA ends, and stop the [[DNA repair]] systems in the cell from treating them as damage to be corrected.<ref name=Nugent>{{cite journal | vauthors = Nugent CI, Lundblad V | title = The telomerase reverse transcriptase: components and regulation | journal = Genes & Development | volume = 12 | issue = 8 | pages = 1073–85 | date = April 1998 | pmid = 9553037 | doi = 10.1101/gad.12.8.1073 | doi-access = free }}</ref> In [[List of distinct cell types in the adult human body|human cells]], telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.<ref>{{cite journal | vauthors = Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW | title = Normal human chromosomes have long G-rich telomeric overhangs at one end | journal = Genes & Development | volume = 11 | issue = 21 | pages = 2801–09 | date = November 1997 | pmid = 9353250 | pmc = 316649 | doi = 10.1101/gad.11.21.2801 }}</ref>

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a [[guanine tetrad]], form a flat plate. These flat four-base units then stack on top of each other to form a stable [[G-quadruplex]] structure.<ref name=Burge>{{cite journal | vauthors = Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S | title = Quadruplex DNA: sequence, topology and structure | journal = Nucleic Acids Research | volume = 34 | issue = 19 | pages = 5402–15 | year = 2006 | pmid = 17012276 | pmc = 1636468 | doi = 10.1093/nar/gkl655 }}</ref> These structures are stabilized by hydrogen bonding between the edges of the bases and [[chelation]] of a metal ion in the centre of each four-base unit.<ref>{{cite journal | vauthors = Parkinson GN, Lee MP, Neidle S | title = Crystal structure of parallel quadruplexes from human telomeric DNA | journal = Nature | volume = 417 | issue = 6891 | pages = 876–80 | date = June 2002 | pmid = 12050675 | doi = 10.1038/nature755 | bibcode = 2002Natur.417..876P | s2cid = 4422211 }}</ref> Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.<ref>{{cite journal | vauthors = Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T | s2cid = 721901 | title = Mammalian telomeres end in a large duplex loop | journal = Cell | volume = 97 | issue = 4 | pages = 503–14 | date = May 1999 | pmid = 10338214 | doi = 10.1016/S0092-8674(00)80760-6 | citeseerx = 10.1.1.335.2649 }}</ref> At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This [[Triple-stranded DNA|triple-stranded]] structure is called a displacement loop or [[D-loop]].<ref name=Burge />

=== Branched DNA ===
{{further|Branched DNA|DNA nanotechnology}}
<div class="thumb tright" style="background:#f9f9f9; border:1px solid #ccc; margin:0.5em;">
{| border="0" cellpadding="2" cellspacing="0" style="width:200px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
|[[File:Branch-dna-single.svg|95px]]
|[[File:Branch-DNA-multiple.svg|95px]]
|-
|align=center|Single branch
|align=center|Multiple branches
|}
<div style="border: none; width:200px;font-size: 90%;"><div class="thumbcaption">[[Branched DNA]] can form networks containing multiple branches.</div></div></div>
In DNA, [[DNA end#Frayed ends|fraying]] occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.<ref>{{cite journal | vauthors = Seeman NC | title = DNA enables nanoscale control of the structure of matter | journal = Quarterly Reviews of Biophysics | volume = 38 | issue = 4 | pages = 363–71 | date = November 2005 | pmid = 16515737 | pmc = 3478329 | doi = 10.1017/S0033583505004087 }}</ref> Branched DNA can be used in [[nanotechnology]] to construct geometric shapes, see the section on [[#Uses in technology|uses in technology]] below.

=== Artificial bases ===
{{Main|Nucleic acid analogue}}

Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named [[Hachimoji DNA]]. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there is nothing special about the four natural nucleobases that evolved on Earth.<ref>{{cite journal | vauthors = Warren M |title=Four new DNA letters double life's alphabet | journal = Nature |date=21 February 2019 | doi = 10.1038/d41586-019-00650-8 | pmid = 30809059 | volume=566 | issue = 7745 | page=436| doi-access = free | bibcode = 2019Natur.566..436W }}</ref><ref>{{cite journal| vauthors = Hoshika S, Leal NA, Kim MJ, Kim MS, Karalkar NB, Kim HJ, Bates AM, Watkins NE, SantaLucia HA, Meyer AJ, DasGupta S, Piccirilli JA, Ellington AD, SantaLucia J, Georgiadis MM, Benner SA | display-authors = 6 |title=Hachimoji DNA and RNA: A genetic system with eight building blocks (paywall)|journal=[[Science (journal)|Science]] |volume=363 |issue=6429 |pages=884–887 |date=22 February 2019 | doi = 10.1126/science.aat0971 | pmid = 30792304 | pmc=6413494 | bibcode=2019Sci...363..884H}}</ref> On the other hand, DNA is tightly related to [[RNA]] which does not only act as a transcript of DNA but also performs as molecular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding [[RNA]],<ref>{{cite journal | vauthors = Burghardt B, Hartmann AK | title = RNA secondary structure design | journal = Physical Review E | volume = 75 | issue = 2 | pages = 021920 | date = February 2007 | doi = 10.1103/PhysRevE.75.021920 | pmid = 17358380 | url = https://link.aps.org/doi/10.1103/PhysRevE.75.021920| arxiv = physics/0609135 | bibcode = 2007PhRvE..75b1920B | s2cid = 17574854 }}</ref> while a higher number is also possible but this would be against the natural [[principle of least effort]].

===Acidity===
The phosphate groups of DNA give it similar [[acid]]ic properties to [[phosphoric acid]] and it can be considered as a [[Acid strength|strong acid]]. It will be fully ionized at a normal cellular pH, releasing [[proton]]s which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by [[hydrolysis]] by repelling [[nucleophile]]s which could hydrolyze it.<ref name="Reusch">{{cite web | vauthors = Reusch W |title=Nucleic Acids |url=https://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/nucacids.htm |publisher=Michigan State University |access-date=30 June 2022}}</ref>

===Macroscopic appearance===
[[File:Estrazione DNA (cropped).jpg|thumb|Impure DNA extracted from an orange]]

Pure DNA extracted from cells forms white, stringy clumps.<ref>{{cite web |title=How To Extract DNA From Anything Living |url=https://learn.genetics.utah.edu/content/labs/extraction/howto/ |publisher=University of Utah |access-date=30 June 2022}}</ref>